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PAX8/PPAR? rearrangement in thyroid nodules predicts follicular-pattern
carcinomas, in particular the encapsulated follicular variant of papillary
carcinoma
#MMPMID24798894
Armstrong MJ
; Yang H
; Yip L
; Ohori NP
; McCoy KL
; Stang MT
; Hodak SP
; Nikiforova MN
; Carty SE
; Nikiforov YE
Thyroid
2014[Sep]; 24
(9
): 1369-74
PMID24798894
show ga
BACKGROUND: PAX8/PPAR? rearrangement is a common genetic alteration in follicular
thyroid carcinoma (FTC) and has been reported with variable frequency in
papillary thyroid carcinoma (PTC). The diagnostic and phenotypic features of
thyroid nodules positive for PAX8/PPAR? on preoperative examination are not well
understood. METHODS: The prevalence of PAX8/PPAR? rearrangement was analyzed in a
series of 2015 consecutive thyroid nodules that underwent molecular analysis on
cytology specimens and in 446 surgically removed PTCs. For all PAX8/PPAR?
positive cases, cytology and surgical pathology slides were examined and the
available clinical records were reviewed. RESULTS: Twenty-two PAX8/PPAR?
rearrangements were identified, including 16 detected preoperatively and 6
postoperatively. The incidence of PAX8/PPAR? in PTC was 1.1%. Cytologically, most
of these nodules were diagnosed as a follicular neoplasm (73%), followed by the
diagnosis of atypia of undetermined significance (19%), and none of the cases was
diagnosed as cytologically malignant. All nodules with PAX8/PPAR? detected
preoperatively and surgical follow-up available were found to be malignant, among
which the most common diagnosis was the encapsulated follicular variant of PTC.
Overall, among 20 PAX8/PPAR?-positive tumors that were surgically excised, 17
(85%) were PTC and 3 (15%) were FTC. On follow-up available for 17 patients
(mean, 22.4 months), 16 PAX8/PPAR?-positive cancers showed no evidence of
biochemical or structural recurrence, whereas 1 patient with FTC developed bone
metastasis. CONCLUSIONS: In this series, PAX8/PPAR? rearrangement found in
thyroid nodules had a 100% predictive value for differentiated thyroid cancer,
and was more predictive of PTC than FTC. However, almost all PTC carrying
PAX8/PPAR? were encapsulated follicular-pattern tumors, distinguished from FTC
only by nuclear features. Although most tumors carrying this mutation appear to
be clinically indolent, at least on short-term follow-up, distant metastasis can
develop from FTC positive for PAX8/PPAR?.
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